Plasmodium ovale is generally thought of as having a relatively limited distribution, with endemic transmission traditionally described as being limited to areas of tropical Africa, New Guinea, the eastern parts of Indonesia, and the Philippines. However, P. ovale infections have also been reported from the Middle East, the Indian subcontinent, and parts of Southeast Asia. In West Africa (and to a lesser extent Central Africa), age specific prevalence (based on light microscopy, LM) of >10% has been observed. However, in most places where P. ovale is observed, it is relatively uncommon and its prevalence (as detected by LM) rarely exceeds 3–5%. As is the case for P. malariae and P. falciparum, P. ovale infections in West African populations tend to be most common in children under ten years of age. Little is known about the potential for interaction between P. ovale and other malaria infections. However, the fact that P. ovale has been found to be most prevalent in areas of West Africa where P. vivax is nearly absent because of the virtual absence of the Duffy blood-group-antigen, which P. vivax requires to invade red blood cells, might indicate a negative interaction between these two species. (Mueller et al. 2007 and references therein) Recent work indicates that there are likely two distinct Plasmodium species that have both been referred to as P. ovale (Sutherland et al. 2010; Oguike et al. 2011)

LikeP. vivax, P. ovale has long been thought to have a dormant stage "hypnozoite" stage that can persist in the liver and cause relapses by invading the bloodstream weeks (or even years) later, but Richter et al. (2010) have questioned whether such a stage actually exists for P. ovale.

The human malaria parasite life cycle involves two hosts, a mosquito and a human. The life cycle is very complex, including both sexual and asexual phases (see life cycle diagram) and involves a stage in the liver as well as the blood stage, the latter being responsible for the clinical manifestations of the disease. (Centers for Disease Control Parasites and Health website)